Women, their Offspring and iMproving lifestyle for Better cardiovascular health of Both.

The WOMB project is a follow-up study of the Lifestyle study that was set up to investigate the costs and effects of a structured lifestyle program in overweight and obese subfertile couples to prevent unnecessary treatment and improve reproductivlifee outcome. Both women and their offspring will be part of the WOMB project.

This part only contains study information about the follow-up of the women who participated in the Lifestyle study (WOMB women). Click for more information about WOMB kids or go to the WOMB website or the website of the Lifestyle study.

RationaleDespite advances in our understanding of the determinants of atherosclerosis, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality across the globe. CVD has traditionally been considered primarily a male disorder, and it is still commonly considered to affect mostly males. However, in Europe, CVD is responsible for 54% of deaths in women, compared to 43% in men. This sex difference in the prevalence of CVD cannot be explained by a sex difference in traditional biological risk factors. Although clinical manifestations of CVD develop about 10 years later in women than in men, it is the major cause of death in women.

Evidence is increasing that pregnancy may be considered as a stress test for future cardiovascular risk. Hypertensive pregnancy disorders have been shown to be strong predictors of hypertension and CVD events later in life. Relative risks that are reported in recent meta-analyses are impressive and of major concern: women who had pre-eclampsia had a 2.06 times higher risk of ischemic heart disease than normotensive counterparts. Further, impaired glucose tolerance during pregnancy and gestational diabetes are female-specific risk factors for the development of type 2 diabetes and the metabolic syndrome at relatively young age. The obstetric history is not yet included in the guidelines for CVD prevention in women, despite these striking figures. Thus far, most female-specific risk factors are not included in the guidelines for CVD prevention in women, as their causative impact on women’s risk and their added predictive values to the current components of the guidelines are still not elucidated. Consequently, pregnancy seems to be a unique window of opportunity to prevent CVD in two generations and potentially beyond. We hypothesize that, in obese women, optimizing lifestyle before fertility treatment or spontaneous pregnancy, improves long term women’s health.

ObjectiveTo investigate the effect of a preconception lifestyle program (aimed at weight loss of 5-10% of the original body weight) for subfertile women with a BMI of 29 kg/m˛ or more, on cardiovascular, metabolic, reproductive and mental health, 4-6 years after lifestyle intervention.

Study designFollow up of a multicenter randomized clinical trial, the Lifestyle study. The WOMB women includes the initial follow-up by (online) questionnaires. Thereafter, women will be asked to participate in a further follow-up by a clinical visit.

Study populationThe study population (N = 578) comprises all women who participated in the Lifestyle study. These women were subfertile and had a body mass index of 29 kg/m˛ or more. They were randomly allocated to six-months during structured Lifestyle program (N = 290) preceding conventional fertility care or to immediate conventional fertility care (N = 288). Due to loss of follow up and withdrew of informed consent in the intervention group (N=10) and control group (N=3) there will be a total of 565 women who are eligible for follow-up (N=280 in the intervention arm vs. N=285 in the control arm). In WOMB women we will ask women with a current or recent pregnancy to participate 6 months post-partum.

MethodsObservational follow-up study women who participated in the Lifestyle study.

Power/data analysisWe will compare BMI, between the women in the intervention arm and those in the control arm using intention to treat analyses. With an alpha level of 5% and an SD of 1.2, we would have an 80% power to detect a 0.5 unit difference in BMI (28 in one group 27.5 in the other) with 90 women in each arm participating in the follow-up. With higher participation rates, we would be able to detect even smaller differences in BMI.

Time scheduleStart recruitment: spring 2015Planned duration of the study: 4 years